Neurologic complications of celiac disease

Dr. Miranda of Weill Medical College of Cornell University has no relevant financial relationships to disclose.

)Russell L Chin MD (Dr. Chin of Weil Medical College of Cornell University has no relevant financial relationships to disclose.)Francesc Graus MD PhD, editor. (Dr. Graus of the University of Barcelona has no relevant financial relationships to disclose.)Originally released March 26, 2018; expires March 26, 2021

Celiac disease is an autoimmune condition triggered by exposure and reaction to gluten with evidence of enteropathy on small intestinal biopsy. It can lead to an array of clinical symptoms, with up to 22% of patients exhibiting neurologic or psychiatric symptoms, most commonly ataxia and peripheral neuropathy. Rarer complications include epilepsy and myopathy, among others. In gluten sensitivity, patients react negatively to gluten consumption but do not necessarily have the hallmark pathology seen in the small intestine. In gluten sensitivity, patients may also exhibit neurologic symptoms.

Up to 22% of patients with celiac disease develop neurologic or psychiatric dysfunction. Some initially present with these symptoms or other extraintestinal manifestations of the disease and may lack small intestine pathology (Briani et al 2008). However, there are several serological screening markers that aid in celiac disease diagnosis, including anti-transglutaminase (tTG), anti-endomysial (EMA), and anti-gliadin antibodies (AGA). Human leukocyte antigen (HLA) typing also shows HLA-DQ2 or HLA-DQ8 in the vast majority of patients with celiac disease (Dieli-Crimi et al 2015). An additional HLA, DQ9, was associated with celiac disease (Bodd et al 2012). Discovery of these clinical, histological, serological, and genetic features supports a celiac disease diagnosis.

Beyond celiac disease, additional immune-mediated disorders relating to gluten have been observed. Gluten allergy is an IgE-mediated immune reaction characterized by asthma and various dermatological symptoms. In cases of gluten sensitivity, as in cases of celiac disease, patients react negatively to gluten consumption and benefit from a gluten-free diet. Gluten sensitivity is 6 times more prevalent than celiac disease and is likely mediated by innate immune mechanisms rather than adaptive ones (Hadjivassiliou et al 2002b; Sapone et al 2011). Small intestine biopsy is normal, and serologies are often negative, although up to 40% of patients have positive AGA titers (Kaukinen et al 2000; Hadjivassiliou et al 2004; Sapone et al 2012). Further, about 50% of patients have HLA DQ2 or DQ8 present, which is significantly higher than the general population (Bizzaro et al 2012).

Patients with gluten sensitivity, like those with celiac disease, often present with extraintestinal symptoms, which is integral in our understanding of the pathophysiology of neurologic complications seen in gluten-related immune disease. Specifically, several studies demonstrate direct immune activity in muscle, peripheral nerves, dorsal root ganglia, spinal cord, brainstem, cerebellum, and brain (Hadjivassiliou et al 2006a; Hadjivassiliou et al 2010a; Leeds et al 2011; Hadjivassiliou et al 2014). This suggests that neurologic complications in gluten-related disorders result from immune-mediated mechanisms rather than being sequelae of enteropathy, such as vitamin and nutrient malabsorption. In fact, the majority of patients with gluten-related disease who present with neurologic complications lack gastrointestinal symptoms (Hadjivassiliou et al 2014).

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.